Calcitonin Gene-related Peptide Levels in Chronic Migraine
Study Details
Study Description
Brief Summary
Twenty patients will be enrolled in a 2-site, 7-month, double-blind study conducted to evaluate a reduction in headache days and attacks and calcitonin gene-related peptide (CGRP) levels in saliva following treatment with OnabotulinumtoxinA versus saline.
Eligible patients will be randomized and receive injections of OnabotulinumtoxinA or Saline at Visit 1. Following 3 months plus a 1 month wash out, patients will receive cross-over injections at Visit 5.
Patients will return for monthly visits and exit the study at Visit 8.
Patients will collect saliva at monthly intervals and document in a daily headache diary throughout the study .
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
This double-blind study will evaluate reduction in number of headache days following treatment with OnabotulinumtoxinA versus Saline. Additionally, CGRP levels in saliva will be correlated with a reduction in headache attacks.
At Visit 1, eligible subjects will be randomized 1:1 to receive injections of OnabotulinumtoxinA or Saline in an identical manner. Subjects will collect 3 saliva samples during each month of the 7 month study: 1 collection at Baseline headache level, 1 collection at onset of headache that is one degree worse than Baseline level that will be treated with acute therapy, and 1 collection at 2 hours following treatment. Subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits.
Following 4 months (including a 1 month washout after Visit 4), subjects will return at Visit 5 and receive cross-over injections. Subjects randomized to OnabotulinumtoxinA at Visit 1 will receive injections of Saline. Subjects randomized to saline at Visit 1 will receive injections of OnabotulinumtoxinA. Subjects will document headache and headache symptoms in a daily diary and return to the clinic with diary and saliva samples at monthly visits.
At Visit 8, 3 months following re-injection at Visit 5, subjects will exit the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: OnabotulinumtoxinA Minimum dose of 155 international units (U) OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. |
Drug: OnabotulinumtoxinA
Minimum dose of 155 U OnabotulinumtoxinA Purified Neurotoxin Complex administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. Subjects will continue to monitor headache symptoms with a headache diary and collect saliva samples as instructed.
At investigator's discretion, additional 40 U OnabotulinumtoxinA Purified Neurotoxin Complex may be administered unilaterally or bilaterally, using follow-the-pain paradigm.
Other Names:
|
| Placebo Comparator: Saline 155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. |
Drug: Saline
155 U Saline administered at 31 fixed-site, fixed-dose injections across seven specific head/neck muscle areas. Subjects will continue to monitor headache using a headache diary and collect saliva samples as instructed.
At investigator's discretion, additional Saline may be administered unilaterally or bilaterally, using follow-the-pain paradigm.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. [Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7]
Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
- Change in Number of Headache Days Per Month From Baseline to Month 1 (M1), Month 1 to Month 2 (M2), and Month 2 to Month 3 (M3). [Baseline (collected historically at screening) vs. Mo 1, Mo 1 vs. Mo 2, Mo 2 vs. Mo 3, Mo 3 vs. Mo 4, Mo 4 vs. Mo 5, Mo 5 vs. Mo 6, and Mo 6 vs. Mo 7]
Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary.
Secondary Outcome Measures
- Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) [Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7]
CGRP Level collected each month when subject did not have a headache or was at lowest pain level of headache that month.
- Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline [For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3]
Saliva samples collected at Baseline (at no headache or lowest level of headache), at headache attack directly before taking rescue medication and 2 hours after treating with rescue medication.
- Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders [For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 at Baseline level (inter-ictal) and at onset of headache that is one degree worse than Baseline level and that will be treated with acute therapy]
Only cytokines with a mean densimetric value 1.65 times the background grey value in a minimum of 3 patients were considered detectable. These are reported below. Values normalized to positive control array spots after background subtraction: C5/C5a, CD40 Ligand, Granulocyte Colony Stimulating Factor (G-CSF), Growth Regulated Oncogene(GRO)-alpha, Soluble Intercellular Adhesion Molecule (sICAM)-1, Interferon gamma (IFN-y), Interleukin(IL)-1alpha, 1beta, 1ra, 8, 16, 17E, & 23, Interferon Gamma-Induced Protein 10 (IP-10), Interferon-inducible T cell alpha chemoattractant (I-TAC), Macrophage Migration Inhibitory Factor (MIF), Serpin E1, and Regulated Upon Activation Normal T-cell Expressed (RANTES)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
must be outpatient, male or female, of any race, between 18 and 65 years of age.
-
if female of childbearing potential must have negative pregnancy test result at Screening Visit and practice reliable method of contraception.
A female is considered of childbearing potential unless she is post menopausal for at least 12 months prior to administration of study drug, without a uterus and/or both ovaries or has been surgically sterilized for at least 6 months prior to study drug administration.
Reliable methods of contraception are: Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study; or, History of bilateral tubal ligation; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or, Any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year (not all IUD's meet this criterion) in use at least 30 days prior to study drug administration; or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm); or, Any other barrier methods (only is used in combination with any of the above acceptable methods) in use at least 14 days prior to study drug administration; or, Any other methods with published data showing that the highest expected failure rate for that methods is less than 1% per year.
-
must have history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society (IHS) for at least 3 months prior to enrollment.
-
must be able to understand the requirements of the study including maintaining a headache Diary, and signing informed consent.
-
must be in good general health as determined by investigator.
-
if taking migraine preventive, must be on a stable dose of preventive medication for at least 3 months prior to screening.
Exclusion Criteria:
-
if female, is pregnant, planning to become pregnant during the study period, is breast feeding, or is of childbearing potential and not practicing a reliable form of birth control.
-
has headache disorders outside IHS-defined chronic migraine definition.
-
has evidence of underlying pathology contributing to their headaches.
-
has any pathology of the salivary glands such as sialadenitis (e.g. Sjogren's syndrome, viral or bacterial sialadenitis) or condition or symptom that would alter the content of saliva.
-
has any medical condition that may increase their risk with exposure to OnabotulinumtoxinA including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function.
-
has profound atrophy or weakness of muscles in the target areas of injection.
-
has skin conditions or infections at any of the injection sites.
-
has allergy or sensitivities to any component of the test medication.
-
who in the opinion of the investigator, has active major psychiatric or depressive disorders including alcohol/drug abuse.
-
meets International Headache Society criteria for Medication Overuse with opioid or butalbital containing products.
-
is planning or requiring surgery during the study.
-
has a history of poor compliance with medical treatment.
-
is currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinvest | Springfield | Missouri | United States | 65807 |
| 2 | Island Neurological Associates, P.C. | Plainview | New York | United States | 11803 |
Sponsors and Collaborators
- Cady, Roger, M.D.
- Allergan
Investigators
- Principal Investigator: Roger K Cady, MD, Clinvest
Study Documents (Full-Text)
None provided.More Information
Publications
- Bellamy JL, Cady RK, Durham PL. Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients. Headache. 2006 Jan;46(1):24-33.
- Bruno PP, Carpino F, Carpino G, Zicari A. An overview on immune system and migraine. Eur Rev Med Pharmacol Sci. 2007 Jul-Aug;11(4):245-8. Review.
- Cady RK, Vause CV, Ho TW, Bigal ME, Durham PL. Elevated saliva calcitonin gene-related peptide levels during acute migraine predict therapeutic response to rizatriptan. Headache. 2009 Oct;49(9):1258-66. doi: 10.1111/j.1526-4610.2009.01523.x.
- Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004 Jan;44(1):35-42; discussion 42-3.
- Munno I, Marinaro M, Bassi A, Cassiano MA, Causarano V, Centonze V. Immunological aspects in migraine: increase of IL-10 plasma levels during attack. Headache. 2001 Sep;41(8):764-7.
- Perini F, D'Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, Bussone G, Toso V. Plasma cytokine levels in migraineurs and controls. Headache. 2005 Jul-Aug;45(7):926-31.
- Sarchielli P, Alberti A, Vaianella L, Pierguidi L, Floridi A, Mazzotta G, Floridi A, Gallai V. Chemokine levels in the jugular venous blood of migraine without aura patients during attacks. Headache. 2004 Nov-Dec;44(10):961-8.
- 10-001AL
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group A | Group B |
|---|---|---|
| Arm/Group Description | Subjects were injected with OnabotulinumtoxinA at Visit 1 (Day 1) and followed for 3 months through monthly office visits (Visits 2, 3, and 4 at Days 31, 61 and 91). Subjects went through a 1 month (30 day) washout period between Visit 4 (Day 91) and Visit 5 (Day 121). Subjects were injected with Saline at Visit 5 (Day 121) and followed for 3 months through monthly office visits (Visits 5, 6, and 7 at Days 151, 181, and 211). | Subjects were injected with Saline at Visit 1 (Day 1) and followed for 3 months through monthly office visits (Visits 2, 3, and 4 at Days 31, 61 and 91). Subjects went through a 1 month (30 day) washout period between Visit 4 (Day 91) and Visit 5 (Day 121). Subjects were injected with OnabotulinumtoxinA at Visit 5 (Day 121) and followed for 3 months through monthly office visits (Visits 5, 6, and 7 at Days 151, 181, and 211). |
| Period Title: First Intervention (90 Days) | ||
| STARTED | 10 | 10 |
| COMPLETED | 9 | 10 |
| NOT COMPLETED | 1 | 0 |
| Period Title: First Intervention (90 Days) | ||
| STARTED | 9 | 10 |
| COMPLETED | 9 | 10 |
| NOT COMPLETED | 0 | 0 |
| Period Title: First Intervention (90 Days) | ||
| STARTED | 9 | 10 |
| COMPLETED | 9 | 10 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Enrolled Participants |
|---|---|
| Arm/Group Description | Enrolled Participants includes subjects in both Group A (treated with BOTOX and Visit 1 and Placebo at Visit 5) and Group B (treated with Placebo at Visit 1 and BOTOX at Visit 5). |
| Overall Participants | 20 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
20
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
48.45
(12.87)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
15
75%
|
| Male |
5
25%
|
| Region of Enrollment (participants) [Number] | |
| United States |
20
100%
|
Outcome Measures
| Title | Change in Number of Headache Days Per Month From Baseline (BL) to Months 1 Through 7. |
|---|---|
| Description | Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary. |
| Time Frame | Baseline (collected historically at screening) versus (vs.) Month (Mo) 1, Mo 2, Mo 3, Mo 4, Mo 5, Mo 6, and Mo 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group A | Group B |
|---|---|---|
| Arm/Group Description | OnabotulinumtoxinA at Visit 1 (headache days in Months 1, 2 and 3) and Saline at Visit 5 (headache days in Months 5, 6 and 7) with washout and crossover at Month 4 | Saline at Visit 1 (headache days in Months 1, 2 and 3) and OnabotulinumtoxinA at Visit 5 (headache days in Months 5, 6 and 7) with washout and crossover at Month 4 |
| Measure Participants | 9 | 10 |
| Baseline vs. Month 1 |
-7.61
(8.01)
|
-6.67
(6.28)
|
| Baseline vs. Month 2 |
-9.72
(5.96)
|
-5.22
(4.44)
|
| Baseline vs. Month 3 |
-10.06
(5.92)
|
-5.22
(5.14)
|
| Baseline vs. Month 4 |
-9.50
(8.34)
|
-6.89
(7.08)
|
| Baseline vs. Month 5 |
-8.94
(8.15)
|
-6.33
(4.12)
|
| Baseline vs. Month 6 |
-9.50
(7.93)
|
-9.22
(5.45)
|
| Baseline vs. Month 7 |
-6.50
(7.53)
|
-4.56
(6.89)
|
| Title | Change in Number of Headache Days Per Month From Baseline to Month 1 (M1), Month 1 to Month 2 (M2), and Month 2 to Month 3 (M3). |
|---|---|
| Description | Baseline number of headache days per month collected historically at screening. Post-treatment number of headache days collected per month via diary. |
| Time Frame | Baseline (collected historically at screening) vs. Mo 1, Mo 1 vs. Mo 2, Mo 2 vs. Mo 3, Mo 3 vs. Mo 4, Mo 4 vs. Mo 5, Mo 5 vs. Mo 6, and Mo 6 vs. Mo 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Group A | Group B |
|---|---|---|
| Arm/Group Description | OnabotulinumtoxinA at Visit 1 (headache days in Months 1, 2 and 3) and Saline at Visit 5 (headache days in Months 5, 6 and 7) with washout and crossover at Month 4 | Saline at Visit 1 (headache days in Months 1, 2 and 3) and OnabotulinumtoxinA at Visit 5 (headache days in Months 5, 6 and 7) with washout and crossover at Month 4 |
| Measure Participants | 9 | 10 |
| Baseline vs. Mo 1 |
-7.61
(8.01)
|
-6.67
(6.28)
|
| Mo 1 vs. Mo 2 |
-2.11
(7.20)
|
1.44
(7.78)
|
| Mo 2 vs. Mo 3 |
-0.33
(3.97)
|
0.00
(1.94)
|
| Mo 3 vs. Mo 4 |
0.56
(3.91)
|
-1.67
(5.66)
|
| Mo 4 vs. Mo 5 |
0.56
(3.21)
|
0.56
(4.61)
|
| Mo 5 vs. Mo 6 |
-0.56
(3.84)
|
-2.89
(5.42)
|
| Mo 6 vs. M 7 |
3.00
(3.84)
|
4.67
(5.63)
|
| Title | Inter-ictal (Baseline) Levels of Saliva Calcitonin Gene-related Peptide (CGRP) |
|---|---|
| Description | CGRP Level collected each month when subject did not have a headache or was at lowest pain level of headache that month. |
| Time Frame | Baseline levels collected for OnabotulinumtoxinA and Saline treatment during Months 1 through 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | OnabotulinumtoxinA | Saline |
|---|---|---|
| Arm/Group Description | This group is a combination of information gathered from both groups while treating with OnabotulinumtoxinA: Group A (Months 1-3) and Group B (Months 5-7). | This group is a combination of information gathered from both groups while treating with Saline: Group A (Months 5-7) and Group B (Months 1-3). |
| Measure Participants | 19 | 19 |
| Treatment Month 1 |
39.64
(7.5)
|
40.79
(9.73)
|
| Treatment Month 2 |
28.37
(7.07)
|
39.14
(9.74)
|
| Treatment Month 3 |
26.14
(3.93)
|
50.63
(15.04)
|
| Title | Saliva CGRP Levels for OnabotulinumtoxinA Responders (Reduction of Headache Days Greater Than 30%) vs. Non-responders and Saline |
|---|---|
| Description | Saliva samples collected at Baseline (at no headache or lowest level of headache), at headache attack directly before taking rescue medication and 2 hours after treating with rescue medication. |
| Time Frame | For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | OnabotulinumtoxinA Responders | OnabotulinumtoxinA Non-Responders | Saline |
|---|---|---|---|
| Arm/Group Description | This group is a combination of information gathered from both groups while treating with OnabotulinumtoxinA: Group A (Months 1-3) and Group B (Months 5-7). Includes subjects with >30% reduction in number of headache days per month when compared to Baseline | This group is a combination of information gathered from both groups while treating with OnabotulinumtoxinA: Group A (Months 1-3) and Group B (Months 5-7). Includes subjects with <30% reduction in number of headache days per month when compared to Baseline | This group is a combination of information gathered from both groups while treating with Saline: Group A (Months 5-7) and Group B (Months 1-3). |
| Measure Participants | 10 | 9 | 19 |
| Treatment Month 1 - Baseline |
52.36
(56.31)
|
29.36
(32.81)
|
70.46
(98.26)
|
| Treatment Month 1 - Attack |
27.94
(21.85)
|
22.36
(20.38)
|
36.23
(33.16)
|
| Treatment Month 1 - 2 Hours Post |
61.55
(44.82)
|
23.66
(12.11)
|
39.76
(54.51)
|
| Treatment Month 2 - Baseline |
59.89
(49.27)
|
28.66
(20.59)
|
44.12
(49.70)
|
| Treatment Month 2 - Attack |
60.14
(51.18)
|
32.65
(33.80)
|
33.05
(30.96)
|
| Treatment Month 2 - 2 Hours Post |
39.13
(60.98)
|
22.35
(19.94)
|
33.93
(35.91)
|
| Treatment Month 3 - Baseline |
51.33
(77.44)
|
32.61
(40.13)
|
58.74
(53.86)
|
| Treatment Month 3 - Attack |
73.18
(58.88)
|
30.17
(38.63)
|
46.16
(40.29)
|
| Treatment Month 3 - 2 Hours Post |
54.04
(34.77)
|
19.11
(13.24)
|
49.39
(43.81)
|
| Title | Changes Between Inter-ictal (Baseline) Levels Between Responders and Non-responders |
|---|---|
| Description | Only cytokines with a mean densimetric value 1.65 times the background grey value in a minimum of 3 patients were considered detectable. These are reported below. Values normalized to positive control array spots after background subtraction: C5/C5a, CD40 Ligand, Granulocyte Colony Stimulating Factor (G-CSF), Growth Regulated Oncogene(GRO)-alpha, Soluble Intercellular Adhesion Molecule (sICAM)-1, Interferon gamma (IFN-y), Interleukin(IL)-1alpha, 1beta, 1ra, 8, 16, 17E, & 23, Interferon Gamma-Induced Protein 10 (IP-10), Interferon-inducible T cell alpha chemoattractant (I-TAC), Macrophage Migration Inhibitory Factor (MIF), Serpin E1, and Regulated Upon Activation Normal T-cell Expressed (RANTES) |
| Time Frame | For OnabotulinumtoxinA and Saline treatment months 1, 2 and 3 at Baseline level (inter-ictal) and at onset of headache that is one degree worse than Baseline level and that will be treated with acute therapy |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of Participants Analyzed is low due to some unusable samples and missing samples making comparison between months impossible. 5 Responders and 5 Non-Responders provided enough samples at all time points for comparisons. |
| Arm/Group Title | Month 1 vs. Saline Responders | Month 1 vs. Saline Non-Responders | Month 3 vs. Saline Responders | Month 3 vs. Saline Non-Responders | Month 1 vs. Month 3 Responders | Month 1 vs. Month 3 Non-Responders |
|---|---|---|---|---|---|---|
| Arm/Group Description | Fold change between first treatment months with OnabotulinumtoxinA and Saline in subjects with >30% reduction in number of headache days per month from baseline. | Fold change between first treatment months with OnabotulinumtoxinA and Saline in subjects with <30% reduction in number of headache days per month from baseline. | Fold change between third treatment months with OnabotulinumtoxinA and Saline in subjects with >30% reduction in number of headache days per month from baseline. | Fold change between third treatment months with OnabotulinumtoxinA and Saline in subjects with <30% reduction in number of headache days per month from baseline. | Fold change between first and third treatment months with OnabotulinumtoxinA in subjects with >30% reduction in number of headache days per month from baseline. | Fold change between first and third treatment months with OnabotulinumtoxinA in subjects with <30% reduction in number of headache days per month from baseline. |
| Measure Participants | 5 | 5 | 5 | 5 | 5 | 5 |
| C5/C5a |
1.38
(0.23)
|
1.01
(0.90)
|
1.39
(0.80)
|
1.61
(0.54)
|
1.03
(0.57)
|
3.26
(3.35)
|
| CD40 Ligand |
1.09
(0.25)
|
1.26
(0.99)
|
0.98
(0.37)
|
1.31
(0.63)
|
0.91
(0.27)
|
1.22
(0.40)
|
| G-CSF |
0.92
(0.45)
|
0.93
(0.55)
|
0.85
(0.24)
|
0.99
(0.58)
|
1.07
(0.74)
|
1.34
(0.76)
|
| GROa |
1.34
(1.56)
|
3.18
(2.20)
|
1.40
(1.33)
|
1.81
(1.32)
|
1.05
(0.96)
|
0.73
(0.55)
|
| sICAM-1 |
2.60
(2.32)
|
0.61
(0.54)
|
5.99
(6.13)
|
2.00
(1.98)
|
3.99
(3.22)
|
1.51
(0.15)
|
| IFN-y |
1.29
(0.34)
|
0.80
(0.69)
|
1.29
(0.82)
|
1.92
(2.95)
|
0.91
(0.34)
|
1.63
(0.94)
|
| IL-1alpha |
2.30
(1.86)
|
2.88
(4.29)
|
1.50
(0.92)
|
2.14
(3.04)
|
0.86
(0.60)
|
0.81
(0.32)
|
| IL-1beta |
1.63
(0.80)
|
1.12
(1.09)
|
1.38
(1.15)
|
0.51
(0.23)
|
1.15
(0.12)
|
1.03
(0.43)
|
| IL-1ra |
1.13
(0.56)
|
2.02
(2.66)
|
0.96
(0.39)
|
1.90
(1.58)
|
0.88
(0.12)
|
1.30
(0.43)
|
| IL-8 |
1.61
(0.83)
|
1.70
(2.03)
|
2.71
(2.29)
|
1.22
(1.24)
|
4.38
(6.98)
|
2.28
(NA)
|
| IL-16 |
0.91
(0.63)
|
2.07
(1.63)
|
0.75
(0.48)
|
1.97
(1.64)
|
0.98
(0.66)
|
1.10
(0.48)
|
| IL-17E |
0.86
(0.50)
|
1.02
(0.91)
|
1.59
(1.79)
|
0.42
(0.13)
|
1.28
(0.85)
|
1.45
(0.04)
|
| IL-23 |
2.45
(1.85)
|
1.80
(1.55)
|
1.06
(0.12)
|
1.69
(1.54)
|
0.93
(0.01)
|
2.61
(3.34)
|
| IP-10 |
1.32
(1.05)
|
0.95
(0.17)
|
0.86
(0.52)
|
2.76
(2.23)
|
1.55
(1.50)
|
3.11
(2.69)
|
| I-TAC |
1.40
(0.78)
|
0.28
(0.12)
|
1.01
(0.89)
|
0.94
(0.26)
|
0.67
(0.27)
|
3.65
(1.33)
|
| MIF |
3.71
(6.25)
|
9.55
(19.47)
|
2.71
(4.50)
|
8.66
(16.79)
|
0.80
(0.32)
|
1.24
(0.27)
|
| Serpin E1 |
0.98
(0.17)
|
0.70
(0.53)
|
0.70
(0.33)
|
0.90
(0.82)
|
0.76
(0.39)
|
3.16
(3.25)
|
| RANTES |
0.95
(0.41)
|
0.77
(0.28)
|
0.93
(0.41)
|
0.91
(0.27)
|
1.14
(0.21)
|
1.24
(0.26)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Saline | OnabotulinumtoxinA | ||
| Arm/Group Description | Subjects injected with Saline in Group A at Visit 5 (Day 151) and Group B at Visit 1 (Day 1) | Subjects injected with onabotulinumtoxinA in Group A at Visit 1 (Day 1) and Group B at Visit 5 (Day 151) | ||
All Cause Mortality |
||||
| Saline | OnabotulinumtoxinA | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Saline | OnabotulinumtoxinA | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/20 (0%) | 0/20 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Saline | OnabotulinumtoxinA | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/20 (55%) | 15/20 (75%) | ||
| Blood and lymphatic system disorders | ||||
| Contusion of extremity | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Elevated Cholesterol | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Enlarged Lymph Node | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Cardiac disorders | ||||
| Coronary Artery Disease | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Heart Arrhythmia | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Inner Ear Fluid Imbalance | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Otitis | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Diverticulitis | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Gastroenteritis | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Influenza | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Parotid Glad Infection | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Salivary Gland Infection | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Salivary Gland Obstruction | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Vomiting | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| General disorders | ||||
| Chest Pain | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Chills | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Head Pain | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Head Tenderness | 0/20 (0%) | 0 | 1/20 (5%) | 2 |
| Hoarseness | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Pyrexia | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Scalp Pain | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Stress | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Vertigo | 1/20 (5%) | 1 | 1/20 (5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Eyebrow Ptosis | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Neck Pain | 0/20 (0%) | 0 | 5/20 (25%) | 5 |
| Shoulder Pain | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Nervous system disorders | ||||
| Fibromyalgia Pain | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Headache | 1/20 (5%) | 1 | 1/20 (5%) | 1 |
| Paresthesia as Injection Site | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Somnolence | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Psychiatric disorders | ||||
| Depression | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchitis | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Cough | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Respiratory Congestion | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Sinus Disorder | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Sinusitis | 4/20 (20%) | 4 | 1/20 (5%) | 1 |
| Upper Respiratory Track Infection | 0/20 (0%) | 0 | 2/20 (10%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| 1st Degree Burn on Extremity | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| 2nd Degree Burn on Extremity | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Cellulitis | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Facial Edema | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Herpes Zoster | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Oral Lesion | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Pharyngitis Streptococcal | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Pharyngolaryngeal Pain | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Pruritus | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Rash | 1/20 (5%) | 1 | 2/20 (10%) | 2 |
| Surgical and medical procedures | ||||
| Dental Implant | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Ruptured Breast Implant | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jeanne Tarrasch |
|---|---|
| Organization | Clinvest |
| Phone | 417-841-3673 |
| jtarrasch@clinvest.com |
- 10-001AL